Fig. 1.

Transgenic overexpression of EAAT2 protects against mutant tau-mediated pathology. a–c Results of behavioral analysis (n = 13/13/10/10, respectively). rTg4510 mice show working memory deficits in the Y-maze (a) and recognition memory deficits in the NORT (b), but EAAT2 overexpression protected against these cognitive deficits. c However, EAAT2 overexpression did not protect against open-field hyperactivity behavior in rTg4510 mice. d, e Biochemical assessment of tripartite synapse pathology (n = 4/group). d As expected, EAAT2 transgenic mice expressed more EAAT2 in gliosomes than wild-type mice, but, unexpectedly, rTg4510 mice express even more EAAT2. rTg4510 × EAAT2 mice paradoxically exhibit reduced EAAT2 in gliosomes, partially normalizing EAAT2 towards control levels. e Synaptic integrity was reduced in rTg4510 mice (as assessed by PSD-95) in synaptosomes, while EAAT2 overexpression protected against synaptodegeneration. f NeuN immunohistochemistry showed that EAAT2 overexpression provided modest protection against neurodegeneration in rTg4510 mice. g Quantification of NeuN immunostaining. h Overexpression of EAAT2 in rTg4510 mice did not alter total tau, phosphorylated tau, or Sarkosyl-insoluble tau aggregates. *P < 0.05, **P < 0.01, P < 0.001